Pathogenesis of meningitis: experimental studies on the molecular basis of Haemophilus influenzae infection.

The successful development and implementation of rational strategies for the prevention of bacterial meningitis should be facilitated by acquiring a more detailed knowledge of its pathophysiology. We have used a biologically relevant rat model of meningitis in conjunction with classical microbial genetics and recombinant DNA technology to investigate the molecular basis of Haemophilus influenzae pathogenicity. These studies aim to define how specific bacterial genes mediate the potential of H. influenzae to colonize the nasopharynx, disseminate within the blood stream and invade the central nervous system. By identifying the state or stages in the pathogenic sequence for which the determinant is critical, this approach should also provide insight into the relevant host defense mechanisms which determine resistance or susceptibility. An understanding of the genetic basis of H. influenzae pathogenicity may develop basic knowledge relevant to the treatment and prevention of bacterial meningitis.